This proposal is part of an ongoing effort to restore sight to the blind with a thalamic visual prosthesis. The proposed research will lay the groundwork for the next major step in the project by demonstrating artificial sight in an animal model, and building tools to design, analyze, and test the performance of a visual prosthesis device that uses thalamic microstimulation. This device has microelectrodes placed in the lateral geniculate nucleus of the thalamus, part of the brain that relays signals from the eye to the rest of the visual system. With results from this proposal we will have in hand a prototype prosthesis in an animal model and be able to predict how experimental designs will perform in blind human subjects. Specific Aim 1 is to measure the visual acuity of normal sighted human volunteers using a virtual reality (VR) simulation of sight as it might appear to a blind patient through an implanted thalamic visual prosthesis. Acuity under various device parameters such as contact count and distribution will be assessed using a letter identification task analogous to standard optometry eye charts and expressed in standard 20/xx notation. We expect to find that a relatively simple device will provide reasonable levels of restoration of function. Specific Aim 2 is to make the same measurements with normal, sighted non-human primates (NHP), creating a foundation for comparing visual prosthesis designs between humans and NHP. We expect to find that non-human primates will perform nearly identically to humans on this task. Specific Aim 3 is to construct prototype prosthesis by adapting the output phase of the VR simulation to multichannel stimulators driving multicontact electrodes, and implant them in NHPs. Importantly; the implants will not affect normal sight so that visual prostheses can be readily calibrated. To evaluate implanted devices, we will use the same letter identification task. We expect to find that the VR models will do a good job of predicting performance with an actual device. With the results of these Specific Aims, we will be prepared to create a prototype visual prosthesis suitable for implanting in a blind volunteer. PUBLIC HEALTH RELEVANCE: Blindness is faced by millions of people due to diseases of the eye like glaucoma, retinitis pigmentosa and macular degeneration, or trauma to the eye from accidents or military combat. A visual prosthesis device to restore sight to these millions of people could be made by sending the output of a digital camera to the visual part of the brain. As proposed here, an important step in making a device like that is to understand how complicated it needs to be in order to be useful and to test a prototype in an animal model.